Abstract
Background: Glioblastoma Multiforme (GBM) is the most common and lethal primary tumor of the brain. GBM is associated with one of the worst 5-year survival rates among all human cancers, despite much effort in different modes of treatment. Results: Here, we demonstrate specific GBM cancer phenotypes that are governed by modifications to the MAPAKAP network. We then demonstrate a novel regulation mode by which a set of five key factors of the MAPKAP pathway are regulated by the same microRNA, hsa-miR-9. We demonstrate that hsa-miR-9 overexpression leads to MAPKAP signaling inhibition, partially by interfering with the MAPK14/MAPKAP3 complex. Further, hsamiR-9 overexpression initiates re-arrangement of actin filaments, which leads us to hypothesize a mechanism for the observed phenotypic shift. Conclusion: The work presented here exposes novel microRNA features and situates hsa-miR-9 as a therapeutic target, which governs metastasis and thus determines prognosis in GBM through MAPKAP signaling.
| Original language | English |
|---|---|
| Pages (from-to) | 23170-23181 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 17 |
| DOIs | |
| State | Published - 26 Apr 2016 |
Bibliographical note
The results published here are fully or partially based on data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI. Information about TCGA and the investigators and institutions constituting the TCGA research network can be found at the project website (http://cancergenome.nih.gov/).Keywords
- Cytoskeleton
- Glioblastoma
- MAPKAP signaling
- Metastasis
- Pathways
- hsa-miR9
